Eligibility
The trial
Local study conflicts
- Co-enrolment to an observational study is permitted but not to another clinical trial of a medicinal product (CTIMP)
Inclusion Criteria:
All of:
- Age ≥ 18 years
- Clinically suspected or proven infection resulting in principal reason for acute illness
- SBP < 90 mmHg or MAP of < 65 mmHg
- Measured serum lactate of >2 mmol/L at the time of eligibility assessment (Nb The serum lactate should be measured 2 hours prior to determination of eligibility, where possible. Longer timeframes may be used and justified within the medical notes if, in the opinion of the investigator, the clinical status of the patient has not significantly improved in the time interval between lactate measurement and eligibility assessment. Lactate measurements more than 4 hours prior to eligibility assessment should not normally be used.)
- Hospital presentation within last 12 hours
Exclusion Criteria:
- >1500ml of intravenous fluid prior to screening
- Clinically judged to require immediate surgery (within one hour of eligibility assessment);
- Immediate (<1 hour) requirement for central venous access
- Chronic renal replacement therapy
- Known allergy/adverse reaction to norepinephrine
- Palliation / end of life care (explicit decision by patient/family/carer in conjunction with clinical team that active treatment beyond symptomatic relief is not appropriate)
- Previous recruitment in the trial
- Patients with permanent incapacity
- Pregnancy. All women of childbearing potential (WoCBP) must have a negative urine or serum pregnancy test result completed as part of screening requirements. WoCBP are defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- Other primary causes of shock (e.g. suspected cardiogenic shock, haemorrhagic shock, etc)
- History or evidence of any other medical, neurological or psychological condition that would expose the subject to an undue risk of a significant Adverse Effect as determined by the clinical judgement of the investigator
- Participation in other clinical trials of investigational medicinal products
- Nb. Please note that the patients vital signs and intake of intravenous fluids may fluctuate. However, it is those vital signs and intravenous fluids reviewed at the time of eligibility that determine entry into the trial.
If the patient is eligible:
Explain that the patient may be eligible for the EVIS study.
Gain verbal agreement in principle before proceeding. Explain:
- Taking part in research is likely to improve the quality of their care
- Risks are carefully controlled - research is safe
- Explain the uncertainty that exists with respect to treatment of their condition;
- If they change their mind they can withdraw their participation at any point
Step-by-Step Guide to Recruitment:
In the working hours of the research team:
- Monday-Friday 07:30 – 18:30
- Contact the EMROx research team on:
Mobile 0776818242
Tel 01865 222003
Bleep 6680
Out of hours, weekends, and when the research nurse is not available:
Estimated time required to enroll
- 20-40 minutes
Eligibility screening
What to do at baseline before randomisation:
- Urine Pregnancy test MUST be negative (if recruits are female).
- Vitals signs.
- Routine blood tests including Lactate (The Lactate is needed for eligibility. A lactate measurement taken within the previous 2 hours can be used, otherwise it must be repeated)
Gather documentation
Documents are downloaded from the EVIS website.
- EVIS
recruitment pack
(includes a copy of the delegation log) - EVIS: Information Sheet for Clinical Staff: INTERVENTION Arm here
- Provide ‘EVIS: Peripheral Norepinephrine Preparation and Administration Record’ to bedside clinical nurses.(found in the recruitment pack)
Formal consent process
If patient is eligible, please consent using either:
- Patient consent
- Personal Representative
- Professional Representative
- Deferred consent (only if other consent not available within 30 minutes).
The decision to defer consent should be made by a doctor at training level ST4 or above or an associate PI or consultant who has appropriate trial training and this should be clearly documented in the medical - Consent forms are accessed online in the EVIS
recruitment pack (Trust login required)
You may need to open https://wiired.org on a Trust desktop computer to be able to print these documents
Randomisation procedure
- Randomisation is carried out on RedCap
https://redcap.clinicaltrials.ed.ac.u
Carrying out the intervention(s):
Arms:
- Usual care – IV crystalloids (approx. 30ml/kg) in the first 3 hours.
- intervention – Peripheral Norepinephine infusion via 20G (pink) cannula or larger peripheral vein + Rescue bolus of 250-500ml of fluids
- Delegated doctor must prescribe the noradrenaline infusion
- Preparation of the infusion: Instructions how to prepare it are found on the Information Sheet for Clinical Staff: INTERVENTION Arm
- Provide the ‘EVIS: Peripheral Norepinephrine Preparation and Administration Record’ to the bedside clinical nurses. Found here in the recruitment pack (Trust login required)
- You may need to open https://wiired.org on a Trust desktop computer to be able to print these documents
Post Randomisation Monitoring and Recording
- Record the total IV fluids volume delivered.
- Record of total IMP delivered and, if delivered, any other vasopressor.
- Continuous monitor for extravasation if IMP is peripheral norepinephrine…
- Patient going to Intensive Care -continue infusion.
- A patient going to a ward can only have the infusion whilst in the ED. Stop the noradrenaline infusion before the patient leaves the ED. Manage Septic shock as per hospital protocol
- Send a message to the EMROx team that the patient was enrolled.
- Ensure that ongoing monitoring is arranged.
Whilst the EMROx team can ensure ongoing monitoring when they are present, at weekends it's important that the clinical team ensure that blood tests set out below are arranges for 24h-, 48h- and 72h-post enrolment.
Whilst an in-patient:
- 6 hours (+/- 1 hour) post randomisation:
- Take and record vital signs (including GCS)
- Record any bloods taken (including lactate) – taking new bloods is OPTIONAL.
- IMP administration
- Record total IV fluids given.
- Record of total IMP delivered and if delivered any other vasopressor.
- Monitor for adverse effects and serious adverse effects
- 12 hours (+/- 4 hours) post randomisation:
- Take and record vital signs (including GCS)
- Record any bloods taken (including lactate) – taking new bloods is OPTIONAL.
- IMP administration
- Record total IV fluids given.
- Record of total IMP delivered and if delivered any other vasopressor.
- Monitor for adverse effects and serious adverse effects
- 24 hour (+/- 6 hours) post randomisation:
- Take and record vital signs (including GCS)
- Take routine bloods (FBC, U&E, LFT, Glucose, CRP – lactate is optional).
- IMP administration
- Record total IV fluids given.
- Record of total IMP delivered and if delivered any other vasopressor.
- Monitor for adverse effects and serious adverse effects
- 48 hour (+/- 12 hours) post randomisation:
- Take and record vital signs (including GCS)
- Take routine bloods (FBC, U&E, LFT, Glucose, CRP – lactate is optional).
- IMP administration
- Record total IV fluids given.
- Record of total IMP delivered and if delivered any other vasopressor.
- Monitor for adverse effects and serious adverse effects
- 72 hours (+/- 12 hours) post randomisation:
- Take and record vital signs (including GCS)
- Take routine bloods (FBC, U&E, LFT, Glucose, CRP – lactate is optional).
- IMP administration
- Record total IV fluids given.
- Record of total IMP delivered and if delivered any other vasopressor.
- Monitor for adverse effects and serious adverse effects
Disposition and follow-up:
- All patients enrolled into this trial will be admitted:
- Patients going to Intensive Care:
- Continue the infusion.
- Patients going to a ward
- Can continue the noradrenaline infusion whilst in the ED.
- Must stop the noradrenaline infusion before the patient leaves ED.
- Otherwise manage Septic shock as per hospital protocol
- Send a message to the EMROx nurses via the whatsapp group that the patient was enrolled.